1. Field of the Invention
The invention relates to water-insoluble polymers useful for preparing bacteriophobic materials and optionally cell proliferation-inhibiting materials, and to processes for the preparation of these polymers. The invention also relates to articles produced using the bacteriophobic materials and optionally cell proliferation-inhibiting materials, and to processes for the preparation of these materials.
2. Description of the Related Art
In all medical examinations, treatments and interventions where articles, instruments or accessories come into direct contact with living tissue and/or body fluids, bacterial contamination can cause considerable difficulties which may even threaten the patient. This applies to short contact just as much to medium-term or long-term applications of implants, catheters, prostheses and other medicotechnical uses. For instance, it is known from P. A. Goldmann, G. B. Pier, Clin. Microbiol. Rev. 6 (1993), 176 ff. that infections in the course of operative interventions may give rise to considerable and costly complications. For the same reasons, catheters need changing after application periods of from 2 to 6 days.
In the field of the food and drink industry, as well, colonization and propagation of bacteria on surfaces of pipelines, containers or packaging are extremely undesirable. In many cases, coats of slime are formed which allow extreme rises in micropopulations, which have a persistent adverse effect on the quality of water, drinks and foods and may even lead to the decay of the product and to damage to the health of the consumers.
Bacteria must be kept away from all fields of life in which hygiene is important. This affects textiles for direct body contact, especially for the genital area and for the care of the elderly and sick. Bacteria must also be kept away from surfaces of furniture and instruments in wards, especially in the area of intensive care and neonatal care, in hospitals, especially in areas for medical interventions, and in isolation wards for critical cases of infection, and also in toilets.
At present, instruments and also surfaces of furniture and textiles are treated against bacteria as required, or else preventatively using chemicals or solutions thereof and using mixtures which, as disinfectants, have a more or less broad and heavy antimicrobial action. Such chemical compositions are nonspecific in their action, are frequently themselves toxic or irritatng, or break down to form products which are objectionable from a health standpoint. In many cases, there are also instances of incompatibility with individuals who are sensitized correspondingly.
A further measure taken against surface bacteria propagation is the incorporation of antimicrobial substances into surface layers, for example the incorporation of silver salts in accordance with WO 92/18098. The incorporation of quaternary ammonium salts into paint-like coatings, moreover, is known from WO 94/13748.
Composites of this kind, however, prove to have little resistance to aqueous solutions or body fluids. Leaching occurs, thereby reducing the concentration of the antimicrobial active substances with the period of application, and lowering the action. Furthermore, when such formulations are used medically, active substance components pass into the physiological circulation, which is extremely undesirable because of toxicological anxieties and potential side-effects.
In a different technical field, U.S. Pat. No. 5,278,200 discloses polymers which comprise carboxylate groups and sulfonate groups in a proportion which is comparable with that of natural heparin. These polymers have anticoagulant properties in relation to thrombocytes in the blood.
Furthermore, diverse attempts are made to immobilize antimicrobial substances on polymeric and/or functionalized surfaces, preferably by means of covalent bonds (T. Ouchi, Y. Ohya, Prog. Polym. Sci., 20 (1995), 211 ff.). In this case chemical bonding to a substrate leads to a reduction in the bactericidal action in comparison with the free active substances. In the case of medical applications, surfaces of this kind often display instances of incompatibility with the physiological system.
In addition, the bacteria which have been killed remain on antimicrobial surfaces and build up organic layers which, ultimately, completely mask the bactericidal actions. The covering of the surface with dead bacteria constitutes a particularly advantageous nutrient base for further microbial infestation (A. Kanazawa, T. Ikeda, T. Endo, J. Polym. Sci. A. Polym. Chem., 31 (1993),1467 ff.).
In the case of certain medical uses, it is not only the bacteriophobic properties of the plastics used that are important but also cell proliferation-inhibiting properties. For example, cell colonization in the case of catheters applied intracorporally in the medium term (indwelling catheters) is just as harmful as in the case of cardiac valves or stents which are implanted for a long period. WO 94/16648 describes a process in which cell sorption and cell propagation on eye implant lenses, which cause clouding of the lens, are prevented by subsequent chemical modification of the surface of the implant. In accordance with EP 0 431 213, polymers are equipped with cell-repelling properties by rendering the surfaces of the polymers hydrophilic using strong mineral acids. This leads to a reduction in cell adhesion.
The subsequent chemical modification of surfaces of polymeric materials is in most cases irregular and/or nonuniform. Untreated areas remain in many cases, and may form starting points for cell colonization of the surface.
The present invention, then, is based on the object of providing a process by which surfaces of polymers can be kept substantially free from bacteria and, optionally at the same time, free from cell colonization in a physiologically compatible manner and without the bacteria which have been killed remaining on the surface. A further object is to provide bacteriophobic and optionally at the same time cell proliferation-inhibiting polymers. Another object of the invention is to provide articles which consist of or comprise certain bacteriophobic and optionally at the same time cell proliferation-inhibiting materials.